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Originally Posted On: https://pauldeleeuwct.wordpress.com/2023/08/16/paul-deleeuws-incretin-weight-loss-newsletter/

Here is an update on the rather fast-moving world of weight loss. After decades of fad diets and ineffective medicines, bariatric doctors now have the use of synthetic incretins. Incretins are normal hormones secreted by the stomach and adjoining structures. Their purpose is to regulate appetite. Semaglutide, a synthetic incretin, has the effect of curbing appetite and slowing digestion. As an injection, it lasts a week (or more). It has side effects, and few people choose to take it for life, but as long as you do take it, you will lose weight.

The weight loss incretin bandwagon is gaining momentum. Eli Lilly is holding its breath waiting for FDA approval of its incretin analog Mounjaro for obesity alone. It is the best of the clinically available weight loss medicines and, since it is already approved for diabetes, has no unusual side effects or other known issues, it should be approved soon. Most users of the once-weekly Mounjaro injection protocol lose 15-20% of their initial weight. Think about that. A lady weighing in at 250 lbs will emerge after treatment at a svelte 200. Inside her body, the 20% difference is immense. Blood sugar goes down. Blood pressure and serum fats also drop. There is a big load taken off her joints, too. Mounjaro, coming soon to a pharmacy near you.Close behind is a brand new incretin drug called retatrutide. This goes even more powerfully forward. Most users lost 25% of their initial weight, and some exceeded 30%. Our obese lady would now end up weighing a mere 175 lbs. Also developed by Lilly, its approval is sure to be delayed because safety has yet to be established. All things considered, it is certainly a promising medicine for the overweight. However, there are a couple of serious issues facing anyone who wants to lose weight this way.1. All these medicines have to be injected. This is expensive, invasive, and painful. Since incretins are rather large molecules, they are typically not absorbed very well orally. Nevertheless, Novo Nordisk has released an oral version of the now classic incretin Semaglutide called Rybelsus. In 50mg doses, it is fully as effective as the injectable version. It does not appear to have any additional side effects, but I am not sure of that as I have not tried it. Currently it is approved only for diabetes, as opposed to simple obesity, but Novo Nordisk is said to be in the paperwork process for its full approval. Peering into the pipeline, we see Lilly’s orforglipron . It is an oral incretin with results similar to Rybelsus but a bit faster acting. It is in “phase 3” trials now, which means that it is a couple of years away from full release. In short, nothing is available orally at this time.2. Insurance coverage for incretins is minimal. The drugs are priced high by the manufacturers, averaging around $1,000/ month. Even at that price, the manufacturers can barely keep up with demand. The reason behind the poor coverage is this: Years ago, a weight-loss drug called Redux, a stimulant, had to be pulled from the market due to toxicity. Medicare took what it saw as the moral high road and refused to pay for ANY weight loss drug. Private insurers, always happy to refuse to pay, followed along. Currently, it is possible for the privately insured to request and receive an exemption to the rule. This is probably because the truly obese are candidates for bariatric surgery, an even more expensive outcome. This may soon change. A recent study of Semaglutide showed that, at high doses, it prevented heart attacks and strokes (see the SELECT study). Even the most callous PBM (Pharmacy Benefit Manager) can hardly fail to see that preventing these serious and costly outcomes is a long-term money saver.3. How fat are you? To see where you stand, you have to learn about the BMI (Body Mass Index). It is a crude measure of obesity, but it is widely accepted and used by insurance companies to gauge the severity of obesity. The NIH (National Institutes of Health) has a web page where you can quickly see your BMI. It is: https://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htmIf you score over 30 but below 35, you are obese. If you are 35 or higher, you are called morbidly obese. The morbidly obese are often referred for bariatric surgery. If your BMI is 30 or higher, it seems to me that you have a good argument to convince the PBM to pay for the incretin medicine you choose. Remember that doctors are fully permitted to prescribe any approved medicine for any use they believe is valid.In the next newsletter, I will discuss staying healthy while taking Incretins.